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Crosstalk between mTOR complexes

Jianling Xie1, Christopher G Proud

  • 1Centre for Biological Sciences, Life Sciences Building (B85), University of Southampton, Southampton SO17 1BJ, UK.

Nature Cell Biology
|November 6, 2013
PubMed

Insights

The mechanistic target of rapamycin (mTOR) pathway involves two complexes, mTORC1 and mTORC2. New findings reveal mTORC1 activation inhibits mTORC2, uncovering a key feedback loop in cellular regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The mechanistic target of rapamycin (mTOR) protein kinase is a central regulator of anabolic processes.
  • mTOR functions within two distinct multi-protein complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).

Purpose of the Study:

  • To elucidate the regulatory relationship between mTORC1 and mTORC2.
  • To investigate the feedback mechanisms governing mTOR signaling pathways.

Main Methods:

  • Utilized biochemical assays to study protein-protein interactions and phosphorylation events.
  • Employed cell-based models to analyze the effects of mTORC1 stimulation on mTORC2 activity.

Main Results:

  • Demonstrated that stimulation of mTORC1 leads to the inactivation of mTORC2.
  • Identified inhibitory phosphorylation of the mTORC2 component, Sin1, as the mechanism mediating mTORC1-induced mTORC2 suppression.
  • Established a negative feedback loop where mTORC1 activity dampens mTORC2 function.

Conclusions:

  • mTORC1 and mTORC2 are integrated into a feedback regulatory circuit.
  • This feedback mechanism, involving Sin1 phosphorylation, provides a novel layer of control over cellular anabolic processes regulated by mTOR signaling.

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